Cryptosporidium causes life threatening enteric disease in HIV-AIDS patients. Immunocompetent individuals are susceptible, but here symptoms are self-limiting. Cryptosporidium is also well known to cause diarrhea in small children. However, the full impact of Cryptosporidium on child mortality and morbidity was only recently appreciated. After rotavirus, Cryptosporidium is the most common pathogen responsible for severe diarrhea in children under 2 years. The main roadblock to achieving urgently needed advances is the overall poor tractability of Cryptosporidium in the laboratory. The goal of this project is to develop genetic tools for this parasite, and the effort builds on ou recent breakthrough in achieving transfection for C. parvum. Specifically, we will use the assay in hand to iteratively optimize transfection vectors and protocols for Cryptosporidium. We will devise strategies to select and isolate stable transgenic parasites from infected animals, and we will use these tools to establish a reporter model for Cryptosporidium. Such reporter pathogens will immediately open the disease to study and establish robust and quantitative correlates of infection, pathogenesis, drug cure, and immune-protection. In the long term, the ability to modify the parasite's genome will enable fundamental discovery and translate into tools and opportunities to treat and prevent cryptosporidiosis.